Article summary with Autism as an adaptive common variant pathway for human brain development by Johnson - 2017

Why should autism not be described as a disorder of neurodevelopment, but rather as a developmental response to atypicalities in early life neural processing?

The diagnostic behavioral symptoms of autism can be viewed as the result of processes of early life adaptation in response to atypical neural signal processing, potentially at the synapse. This sub-optimal quality signal processing may be caused by genetic or environmental effects, sensory limitations, or a combination of factors. A series of compensatory and adaptive processes trigger an alternative trajectory of subsequent development, resulting in the majority of the behavioral phenotype associated with an autism diagnosis. 

What are the advantages of focusing on the whole brain level of description of the nervous system?

To fully understand processes of ontogenetic adaptation, the whole brain should be considered. Evidence should show that distant neural systems and regions can adjust to compensate for poor functioning or damage elsewhere. Also, common developmental disorders are associated with widespread changes in the functioning of large-scale neural networks. 

What is ontogenetic adaptation?

Ontogenetic adaptation refers to a class of processes in which a given individual’s brain maximizes its fit to the environment in ways that may, or may not, result in neurotypical behavioral phenotype. 

Which four types of whole brain adaptation are suspected to lead to the adaptive developmental trajectory that results in autism?

It is hypothesized that poor quality signal processing early in life, mediated through synaptic contacts, leads to the adaptive developmental trajectory that results in autism. This trajectory is thought to be caused by four types of whole brain adaptation that also drive typical developmental trajectory: 

• Redundancy: the existence of duplicated functions or neural systems that can compensate for the loss of another under most circumstances. 
• Reorganization: the reallocation of functions to regions or networks as orchestrated by critical hubs.
• Changes in the timing of developmental trajectories to compensate for poor sampling of information from the early environment.
• Niche construction: the process by which individuals select and construct an environment that best suits their own individual brain’s processing style. 

How can the level of neonatal encephalopathy influence developmental pathways?

Neonatal encephalopathy (NE) is a clinical syndrome of disturbed neurological function, a common secondary consequence of perinatal asphyxia. The typical route is well buffered against mild NE (minor or transient perturbations). Moderate NE (more significant and longer lasting disruption within a sensitive period) can divert development to an alternate pathway in which a different profile of abilities, disabilities, and behaviors can emerge. Severe NE exceeds the limits of adaptation, resulting in slow progression down any developmental pathway with poor life-long outcomes over all domains. 

If general factors drive the neurodevelopmental pathway to autism, how does the apparent domain-specificity of the cognitive and behavioral profile of the syndrome arise?

Three important factors are identified:

• Repetitive behavior. Self-generating predictable stimulation patterns that are easier to successfully compute than many real world events, particularly those in the social domain.
• Focal attention style. An adaptive response that restricts the quantity of information flow to help with parallel processing limits.
• Withdrawal from social contexts. Directing attention and processing resources to more comprehensible aspects of the early environment is more likely to maximize the fit between neural processing capacity and environment.

What are the mechanisms that underlie the adjustments in whole brain systems to accommodate early differences in synaptic processing? 

Two types of whole-brain network adjustment that could underpin ontogenetic adaptation in terms of sensitive periods for human brain development are identified:

• The construction of the structural connectivity network over the first two years may be open to influence by a variety of factors (including the ontogenetic history of brain functioning).
• The less specialized network present in the infant brain allows for a broader mapping between the computations that underlie adaptive behaviors and their implementation across structural neural networks. 

Why are differences in the functioning of specific brain regions associated with autism? 

Hub regions integrate information from different parts of the brain, but they are also vulnerable. Their higher metabolic rate may make them more sensitive to pathogenic effects (such as oxidative stress). Also, these regions are often the focus for convergence and integration of fine spatial and temporal resolution information and are differentially sensitive to small changes in signal-to-noise-ratio or slight E/I imbalances. The importance of these hub regions for coordinating the activity of others may make them harder to compensate for following damage and therefore more likely to be implicated in clinical conditions. 

To what extent is there a sensitive period early in life within which the adaptive changes must occur?

As a syndrome of adaptation, a hallmark of later autism is that the process of brain adaptation is initiated within the first two or three years. Some of the types of early neural disturbance associated with causes of autism could be transient developmental glitches which are restored later. Barker’s hypothesis is very important, stating that fetuses adapt to the environment that they expect to enter postnatally. A mismatch between the prenatal and postnatal environment can be harmful as the body is physiologically prepared for the conditions similar to the prenatal environment. Predictive adaptive responses result in later disorders only when there is a mis-match between the predicted later environment and reality.